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N Grundström

Publications and source records attributed to N Grundström.

At least 37 records · Page 2Linked to original sources
PubMed1989

Characterization of pigment aggregating alpha 2-adrenoceptors of fish melanophores by use of different agonists after partial irreversible receptor inactivation.

1. The affinity for, and the intrinsic efficacy on, postsynaptic melanosome aggregating alpha 2-adrenoceptors of fish melanophores was studied for B-HT 920, clonidine, medetomidine, noradrenaline, phenylephrine and UK-14,304. Investigations were carried out by evaluating the effects of progressive, irreversible inactivation of the alpha 2-adrenoceptors by benextramine. 2. The double reciprocal plots of equieffective concentrations of B-HT 920, clonidine, noradrenaline and phenylephrine were linear, which indicated that these compounds exerted their effects, mainly, through interaction with one receptor site. 3. The affinity for the alpha 2-adrenoceptor selective agonist B-HT 920, was found to be about 1000 times higher than the affinity for the alpha 1-adrenoceptor selective agonist phenylephrine. 4. The corresponding plot of equieffective concentrations of medetomidine was not linear, which may indicate that this imidazole compound exerted its effect through more than one receptor site. However, when phenoxybenzamine was used in place of the more selective benextramine, a linear relationship was obtained.

Adrenergic alpha-Agonists↗
PubMed1989

Both the cholinergic and non-cholinergic components of airway excitation are inhibited by morphine in the guinea-pig.

In order to investigate the effect of morphine on the excitatory and inhibitory non-adrenergic, non-cholinergic (NANC) neurotransmission and cholinergic neurotransmission in airways, ring preparations from guinea-pig trachea and bronchi were studied. The preparations were stimulated by electrical field stimulation to elicit contractions and relaxations. Both cholinergic and NANC contractions were reduced by morphine in a dose-dependent way, while the inhibitory NANC neurotransmission was unaffected. A morphine concentration of 10(-4) M reduced the NANC contractions to 20.8 +/- 1.5% of the control contractions and the cholinergic contractions to 49.7 +/- 4.2%. The effect of morphine on cholinergic neurotransmission was completely inhibited by naloxone (10(-5) M) while the effect of morphine on NANC contractions only was reduced to 67.6 +/- 5.6% of the control contractions. It is suggested that morphine influences the excitatory neurotransmission via pre-junctional sites, since morphine had no effect on the acetylcholine-induced contractions.

Animals↗
PubMed1989

A novel neurogenic vasodilator mechanism in bovine mesenteric artery.

The presence of a neurogenic vasodilator mechanism was investigated in isolated bovine mesenteric arteries (BMAs) that were precontracted with phenylephrine. Electrical field stimulation induced tetrodotoxin-sensitive relaxations in guanethidine-pretreated BMAs. The relaxation occurred after a delay of about 5-8 seconds and amounted to 25-35% in different sets of experiments. The relaxation was not affected by classical receptor antagonists such as atropine (1 microM), cimetidine (3.9 microM), clemastine (2.8 microM), naloxone (1.2 microM), 8-phenyltheophylline (1 microM), propranolol (3.4 microM), ritanserin (5 microM), or droperidol (13 microM). The nicotinic acetylcholine-receptor stimulant 1,1-dimethyl-4-phenyl-piperazinium iodide (10 microM) was without effect on the relaxation, and removal of the endothelium of the arteries also had no effect. The bee venom component apamin (1 microM), which has been shown to block the nonadrenergic, noncholinergic relaxation in intestinal and vascular smooth muscle from other species, was also found to be without effect on the relaxation induced by electrical field stimulation in BMAs. Pretreatment of the arteries with capsaicin (1 microM) had no effect per se and did not affect the relaxation induced by a subsequent stimulation. Capsaicin has been suggested to release neurotransmitter and eventually deplete neurons containing substance P and calcitonin gene-related peptide. Furthermore, exogenously applied calcitonin gene-related peptide (1-100 nM), substance P (10 nM-1 microM), and vasoactive intestinal peptide (0.3-30 nM) gave relaxations amounting to less than 10%. It is postulated that electrical field stimulation induces a neurogenic relaxation of a nonadrenergic, noncholinergic nature in BMAs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Pigment migration in fish erythrophores is controlled by alpha 2-adrenoceptors.

1. The aggregation of erythrosomes within erythrophores of the squirrel fish (Myripristis occidentalis; belonging to the family Holocentridae) was, on pharmacological grounds, shown to be mediated by alpha 2-adrenoceptors. 2. The erythrophores were shown to be controlled by adrenergic nerves activating the alpha 2-adrenoceptors. 3. The erythrophores themselves were found to possess a K+-sensitive mechanism of aggregation. 4. Some similarities and differences of the alpha 2-adrenoceptor-mediated chromatosome aggregation in melanophores and erythrophores are also discussed.

Animals↗
PubMed1988

Relaxation of bovine mesenteric artery induced by glyceryl trinitrate is attenuated by pertussis toxin.

Low concentrations (less than 1 nM) of glyceryl trinitrate (GTN) induced a considerable relaxation of bovine mesenteric arteries (BMA) brought to sustained contraction by the addition of phenylephrine. The concentration-response curve of GTN showed a biphasic pattern with a high and a low affinity component. Pretreatment with pertussis toxin (IAP) attenuated the high affinity relaxant component, but not the low affinity component or the relaxation induced by NaNO2. A polyclonal antibody to IAP counteracted the effect of the toxin on the GTN-response. Low concentrations of GTN increased the cGMP level in BMA via activation of the high affinity pathway. This effect was also inhibited in preparations pretreated with IAP. It is suggested from the present study that GTN induces relaxation of vascular smooth muscle via two separate pathways, the high affinity pathway might involve a receptor-complex interaction with a regulatory protein.

Animals↗
PubMed1988

Effects of an alpha-2 adrenoceptor agonist on angiotensin converting enzyme inhibitor-induced hypotension and potentiated allergen-evoked inflammatory skin responses.

Angiotensin converting enzyme (ACE) inhibitors have been demonstrated to possess proinflammatory properties. Persistent cough and increased broncho-obstruction have been reported frequently in hypertensive subjects on ACE inhibitor therapy. We have studied the effect of an alpha-2 adrenoceptor agonist, clonidine, on MK 422 (active parent diacid of enalapril)-induced hypotension and potentiated inflammatory skin responses in ovalbumin-sensitized guinea pigs. Clonidine was found to abolish dose-dependently MK 422-potentiated ovalbumin-evoked inflammatory dermal responses and it possesses additive hypotensive effects when combined with the ACE inhibitor. It would therefore be interesting to evaluate further alpha-2 adrenoceptor agonists and ACE inhibitors in a combination therapy in humans when single drug antihypertensive therapy of the drugs is insufficient.

Adrenergic alpha-Agonists↗
PubMed1988

Pronounced supersensitivity of postjunctional alpha adrenoceptors after denervation of fish melanophores.

The aggregation of melanosomes within melanophores (pigment cells) attached to isolated scales from the cuckoo wrasse (Labrus ossifagus L.) can be elicited either by stimulation of intrinsic nerves (electrical field stimulation of K+ depolarization) or by adrenoceptor agonists. The melanophores of isolated scales survived in a culture medium for up to 20 days. During this period a progressive increase in sensitivity to exogenously applied noradrenaline took place. After 8 days of isolation there was an about 300-fold increase in sensitivity to noradrenaline. The increased sensitivity was accompanied by a progressive loss of the nerve-elicited response during the first days of isolation. Before and during this early period cocaine was found to potentiate the effect of noradrenaline about 8-fold. On the 3rd day after isolation the effect of cocaine was lost, which coincided fairly well with the time when the nerve-mediated response was lost. The early developing increase in sensitivity to noradrenaline (8-fold) is therefore most likely caused by loss of presynaptic amine uptake, but the main part (50-fold) of the increase in sensitivity presumably has other explanations, like changes in the receptor population.

Adrenergic alpha-Agonists↗
PubMed1987

Innervation of airway smooth muscle. Efferent mechanisms.

The classical view, with one excitatory (cholinergic) and one inhibitory (noradrenergic) component, of the innervation of airway smooth muscle is incomplete and at least two other, possibly peptidergic, types of innervation must be included when the innervation of airways is considered. A summary of these neuronal components is given in Fig. 1 and their possible origin is outlined. Besides the inhibitory noradrenergic innervation of the airways observed in some species, an inhibitory NANC (i-NANC) innervation has been demonstrated. The polypeptide, VIP, seems to be the most likely candidate for the neurotransmitter in the i-NANC innervation of the airways. The excitatory cholinergic innervation is present in the airways from the trachea down to the peripheral bronchi. In the guinea-pig bronchi an excitatory NANC (e-NANC) innervation has been demonstrated as well. The e-NANC nerves may correspond to chemosensitive primary afferent nerves with substance P or a related tachykinin as transmitter. When the innervation of airway smooth muscle of different mammalian species is compared it is evident that all nerve components except the cholinergic, show a considerable variability among species. The cholinergic innervation seems to be present in all mammalian species whereas the other components may be completely absent from some species. Distinct regional variations in the innervation of the airways may occur, which is exemplified by the distribution of the autonomic innervation in the guinea-pig tracheo-bronchial tree. Cholinergic neurotransmission in for example the guinea-pig and human airways can be modulated by NA via prejunctional inhibitory alpha 2-adrenoceptors. Furthermore, the e-NANC neurotransmission in the guinea-pig airways may be modulated by NA or by selective alpha 2-adrenoceptor agonists, acting via prejunctional inhibitory alpha 2-adrenoceptors. The clinical importance of the NANC innervation in relation to asthma is discussed. The i-NANC nerves may exert a modulating effect on bronchoconstriction, and a functional defect would presumably lead to an exaggerated response to constrictor stimuli. The e-NANC nerves in the airways may also be clinically relevant since the transmitter (tachykinins) from these nerves can produce bronchoconstriction and promote inflammation of the airway epithelium, either by direct mechanisms or indirectly by activation of mast cells, and thus contribute to the features of asthma.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Comparative studies on nerve- and noradrenaline-induced melanosome aggregation within different species of fish.

1. The aggregation of melanosomes within melanophores of the cuckoo wrasse (Labrus ossifagus; belonging to the family Labridae) has, on pharmacological grounds, been shown to be mediated by postsynaptic alpha 2-adrenoceptors which in turn act via an inhibitory control of adenylate cyclase. 2. In the present paper we have investigated some American species belonging to the Labridae, Haemulidae, Embiotocidae, Clinidae and Pleuronectidae. 3. In all instances, except in the case of sargo (Haemulidae), we could demonstrate that melanosome aggregation probably was mediated by postsynaptic alpha 2-adrenoceptors which mediate their effect by inhibiting the adenylate cyclase of the melanophores. 4. Although these receptors apparently, on pharmacological grounds, may be classified as alpha 2-adrenoceptors it was also concluded that there is a phylogenetic divergence among these receptors.

Adrenergic alpha-Antagonists↗
PubMed1987

Comparison of the effects of clonidine and guanfacine on the histamine liberation from human mast cells and basophils and on the human bronchial smooth muscle activity.

The inhibitory effects of clonidine and guanfacine on antigen-induced histamine release from human basophils and mast cells and on bronchial muscle tension were compared. Clonidine, but not guanfacine inhibited the antigen-induced histamine release from human basophils and mast cell preparations. This effect of clonidine was prevented by an H2-antagonist, cimetidine. Clonidine and guanfacine, like norepinephrine, inhibited the twitch contraction of electrically stimulated human segmental bronchi by stimulation of alpha 2-adrenoceptors. Clonidine and guanfacine had no effects on the basal bronchial muscle tone, but in very high concentrations they could reduce a carbacholine-induced bronchial tone. It is suggested that the inhibitory effects of clonidine on allergic reactions and on exicitatory nerve transmission in human airways may be useful in the treatment of asthmatic patients.

Adrenergic alpha-Agonists↗
PubMed1985

The effect of pertussis toxin on alpha-2-adrenoceptor-mediated pigment migration in fish melanophores.

The aggregation of melanin-granules within fish pigment cells (melanophores) can be elicited either by electrical stimulation of intrinsic nerves or by the addition of adrenergic agonists. The pigment aggregation seems to be mediated by alpha-2-adrenoceptors. In this investigation we have used various agonists and antagonists (noradrenaline, (+)- and (-)-adrenaline, isoprenaline, yohimbine and prazosin) to further characterize the pigment-aggregating receptor of Labrus ossifagus. All the results obtained support the notion of alpha-2-adrenoceptor-mediated pigment aggregation. The pertussis toxin, islet-activating protein (IAP), is known to inhibit the alpha-2-adrenoceptor-mediated signal transduction in mammals. We have used IAP to investigated whether fish melanophore alpha-2-adrenoceptors are also inhibited by this toxin. We found that IAP inactivated the alpha-2-adrenoceptor-mediated pigment aggregation in a dose-dependent manner. The inhibitory IAP-effect had a remarkably short onset-time in the melanophores (maximal effect was obtained within 10 min of incubation). Interestingly, binding of an agonist (noradrenaline) to the receptors prevented IAP from exerting its inhibitory action, whereas binding of an antagonist (yohimbine) gave no protection against the IAP-inactivation. In conclusion, the pigment-aggregating receptors of melanophores of L. ossifagus are very similar to the mammalian alpha-2-adrenoceptors. It is possible to inactivate the melanophore receptor system with IAP and this inactivation has a remarkably short onset-time. Stimulation of the alpha-2-adrenoceptors prevents IAP from inactivating the receptor system.

Adrenergic alpha-Agonists↗
PubMed1985

In vivo demonstration of alpha-2-adrenoceptor-mediated inhibition of the excitatory non-cholinergic neurotransmission in guinea pig airways.

In anaesthetized guinea pigs, vagal nerve stimulation caused an atropine- and hexamethonium-resistant increase in the respiratory insufflation pressure. Clonidine (0.05 mg/kg i.v.) inhibited the increase in insufflation pressure caused by vagal stimulation. This effect of clonidine was antagonized by the alpha-2-antagonist yohimbine (0.5 mg/kg i.v.), but not by the alpha-1-antagonist prazosin (0.03 mg/kg i.v.). In conclusion, the increase in the respiratory insufflation pressure, caused by stimulation of noncholinergic nerves, seemed to be controlled by inhibitory alpha-2-adrenoceptors in guinea pig airways.

Acetylcholine↗
PubMed1985

The control of granule movement in fish melanophores.

The effects of electrical field stimulation, alpha-2-adrenoceptor activation and manipulation of the intracellular machinery on aggregation and dispersion of melanosomes within melanophores of Labrus ossifagus were studied. Neither melatonin nor MSH exerted any direct effects on the melanophores, and furthermore MSH alone did not affect the responses elicited by electrical stimulation or by noradrenaline. Omitting extracellular Ca2+ blocked the nerve-mediated aggregation but was without effect on noradrenaline-induced aggregation. Colchicine and demecolcine inhibited the melanosome aggregation induced by noradrenaline. The characteristics of aggregation and dispersion were found to diverge in several ways. In melanophores made permeable by dispersion were found to diverge in several ways. In melanophores made permeable by using saponin, cyclic AMP caused dispersion. The dynein-ATP-ase inhibitor vanadate prevented the melanosome aggregation within saponin-treated melanophores, while vandate was without effect on the cyclic AMP-induced dispersion. The melanosome transport in saponin-treated melanophores could be activated even in the absence of Ca2+, indicating that the melanosome movements were completely Ca2+-independent.

Animals↗
PubMed1985

Inhibition of the cholinergic neurotransmission in human airways via prejunctional alpha-2-adrenoceptors.

Previous investigations on guinea-pig airways indicate that the excitatory, cholinergic neurotransmission can be inhibited via prejunctional alpha-2-adrenoceptors. The aim of this study was to investigate whether a similar inhibition of the cholinergic neurotransmission is present in human airways. Ring preparations of human bronchi were mounted for recording of isometric tension and immersed in oxygenated Krebs solution. Electrical field stimulation of the preparations elicited atropine-sensitive twitch contractions. Exogenous noradrenaline (in the presence of cocaine and propranolol) inhibited the electrically evoked contractions. The noradrenaline-induced inhibition could be antagonized by yohimbine whereas prazosin was ineffective, indicating that the inhibition was mediated by alpha-2-adrenoceptors. Contractions evoked by exogenous acetylcholine (in the presence of cocaine and propranolol) was unaffected by the addition of noradrenaline, which suggests that the alpha-2-adrenoceptors have a prejunctional localization. In conclusion, this report gives evidence that the human bronchial, cholinergic neurotransmission can be inhibited by stimulation of prejunctional alpha-2-adrenoceptors.

Acetylcholine↗
PubMed1984

Neuronally mediated non-cholinergic contraction of guinea-pig bronchial smooth muscle is inhibited by a substance P antagonist.

The isolated main bronchi of the guinea-pig respond to electrical field stimulation with a twitch followed by a slow contraction. Atropine blocked the slow contraction. The substance P antagonist, (D-Pro2, D- Trp7 ,9)-SP, greatly reduced the atropine-resistant contraction. The results suggest the involvement of substance P in non-cholinergic neurotransmission in the guinea-pig airways.

Animals↗
PubMed1984

Inhibition of the excitatory non-adrenergic, non-cholinergic neurotransmission in the guinea pig tracheo-bronchial tree mediated by alpha 2-adrenoceptors.

Guinea pig main bronchi were studied in vitro for the presence of motor innervation. Field stimulation of the main bronchi revealed that besides the excitatory cholinergic component a slow and atropine resistant contraction similar to that previously found in the hilus bronchi (Grundström et al. 1981a) was present also at this level of the airways. This slow contraction was blocked by tetrodotoxin whereas it was left unaffected by a number of conventional antagonists (i.e. atropine, guanethidine, propranolol, yohimbine and prazosin) suggesting that it was due to activation of non-adrenergic, non-cholinergic neurones. In the presence of a beta-adrenoceptor blocking drug, noradrenaline inhibited the slow contractions induced by field stimulation in both the main and hilus bronchi. By contrast, contractions elicited by histamine were left unaffected by noradrenaline. In order to characterize the receptor for noradrenaline the effects of alpha1-and alpha2-adrenoceptor blockers were evaluated. The results indicate that in the guinea pig bronchi noradrenaline inhibits non-adrenergic, non-cholinergic neurotransmission by acting on prejunctional alpha 2-adrenoceptors.

Animals↗